Biomedical subjects

Kimberly Brown

Publications and source records attributed to Kimberly Brown.

11 recordsLinked to original sources

PubMed2005

Uncovering histologic criteria with prognostic significance in toxic epidermal necrolysis.

OBJECTIVE: To identify histologic criteria and prognostic significance in patients with toxic epidermal necrolysis (TEN), a frequently lethal disease that usually represents an adverse drug reaction. DESIGN: Retrospective analysis of clinical records and histologic material from a 10-year period (1994-2004). Two investigators blinded to clinical data reviewed hematoxylin-eosin-stained sections. SETTING: North American tertiary care, university-based burn unit. Patients Thirty-seven patients treated for TEN between 1994 and 2004 who had sloughing of 30% or more of their total body surface area and who underwent skin punch biopsies immediately following admission. Main Outcome Measure The degree of dermal mononuclear (DM) inflammation was graded (sparse, moderate, or extensive) at least 2 high-power fields (HPF) away from the perimeter of epidermal detachment, and the mean number of DM cells/5 HPF was quantified for each patient. Clinical records were reviewed and the following data extracted: age, history of cancer, percentage of total body surface area slough, heart rate, and serum glucose, bicarbonate, and serum urea nitrogen values on admission. Severity scores for TEN (SCORTEN) were calculated, and clinical outcome was recorded as survived or died during hospitalization. RESULTS: Extent of inflammation was assessed by categorizing the mean +/- SD DM cell counts as follows: sparse, 161 +/- 36 cells/HPF (n = 15); moderate, 273 +/- 76 cells/HPF (n = 15); and extensive, 392 +/- 124 cells/HPF (n = 7). There was good concordance between observer ratings (P<.001). While 73% of patients (n = 11) with sparse inflammation survived, only 47% (n = 7) with moderate and 29% (n = 2) with extensive inflammation survived. The accuracy in predicting patient outcome was 65% using grade of inflammation, 68% with mean cell count, and 71% with SCORTEN. CONCLUSIONS: There is a histologic spectrum with TEN that ranges from sparse to extensive DM inflammation, and degree of inflammation predicts clinical outcome approximately as well as SCORTEN. Future clinical trials should consider the possibility that various patient subsets exist within the TEN population, and a role for immunocytes needs to be critically reevaluated in this devastating disease.

Adult↗

PubMed2004

Linking TGF-beta-mediated Cdc25A inhibition and cytoskeletal regulation through RhoA/p160(ROCK) signaling.

Transforming growth factor-beta (TGF-beta) can mediate G(1)/S cell-cycle inhibition and changes in the cytoskeletal organization through multiple parallel downstream signaling pathways. Recent findings regarding TGF-beta-mediated cell-cycle checkpoint control and epithelial to mesenchymal transition have converged to the RhoA/p160(ROCK) signaling pathway. The activation of TGF-beta-mediated p160(ROCK)rapidly inhibits the Cdc25A phosphatase as a component of the G(1)/S checkpoint control at the time cytoskeletal re-organization occurs. This can be likened to the ability to preserve genomic integrity in circumstances of genotoxic stress. The inactivation of the RhoA/p160(ROCK) pathway may be a mechanism by which cancer cells bypass growth inhibition even in the presence of TGF-beta.

Animals↗

PubMed2004

The efficacy and limitations of sirolimus conversion in liver transplant patients who develop renal dysfunction on calcineurin inhibitors.

This study evaluates sirolimus in preserving renal function in 28 patients who developed renal insufficiency after liver transplantation. Patients with a creatinine level higher than 1.8 mg/ml were eligible for conversion. Of the 28 patients, 7 (25%) did not tolerate sirolimus, 6 (21%) progressed to end-stage renal disease (ESRD), and 14 (50%) have been maintained on sirolimus with stable renal function. The 28 patients overall had a decline in creatinine of 0.38 mg/dl (P = 0.029) at week 4, with a small increase by week 24. However, the subset of 14 patients who did not develop ESRD had a decline in creatinine that persisted to week 48. While the differences between those who developed ESRD and those with stable renal function were not statistically significant, the patients who developed ESRD had a higher creatinine at conversion (2.8 vs 2.3) and a lower creatinine clearance (36 vs 53 ml/min). Patients receiving sirolimus had a persistent rise in cholesterol (P < 0.05). The use of sirolimus to preserve renal function was limited by patients unable to tolerate drug- (25%) and patients who developed ESRD (21%). A subgroup of patients (50%) had an improvement in creatinine that persisted for 48 weeks.

Calcineurin↗

PubMed2004

An approach to simulation program development.

Simulation education is becoming increasingly popular. Many institutions and programs find themselves in a situation where they have an identified need for the simulation education but few resources to reference. Most programs purchase first and ask questions later, leaving faculty with equipment with which they are unfamiliar and few, if any, resources to contact. Developing a simulation program involves more steps than one would think. Developing a vision and business plan are paramount. Only with a well-developed business plan will decision maker buy-in occur. Consideration must also be given to facility construction or renovation, equipment purchase, faculty development and training, and most important, curriculum development. These steps are not intuitive. This article describes these steps in a concise and manageable way and is intended to serve as a template that hopefully will increase the likelihood of developing successful and efficient simulation education programs.

Computer Simulation↗

PubMed2004

Simulation: not just a manikin.

Simulation education is currently flourishing in the United States and around the world. Simulation technology has improved, and its costs have dropped. When faced with demands for more accountability for quality education and increased enrollment, disciplines and specialties are embracing the idea of simulation as a valuable tool. Frequently, institutions develop simulation programs based on a narrow understanding of the technology and teaching potential of this tool. The purchase of simulation equipment often precedes the development of a sound program "vision" and plan. Only after understanding the tools and equipment can a meaningful plan be developed. This article introduces and clarifies the different types of simulation equipment, and attempts to make sense of the roles and limitations of these technologies. It is through this knowledge that educators and program directors can best develop programs that are educationally meaningful. Similarly, a good understanding of simulation technology and terminology will likely lead to more thoughtful and cost-effective purchases.

Computer Simulation↗

PubMed2003

TGF-beta-induced RhoA and p160ROCK activation is involved in the inhibition of Cdc25A with resultant cell-cycle arrest.

The ability of the transforming growth factor beta (TGF-beta) signaling pathways to inhibit proliferation of most cells while stimulating proliferation of others remains a conundrum. In this article, we report that the absence of RhoA and p160ROCK activity in fibroblastic NIH 3T3 cells and its presence in epithelial NMuMG cells can at least partially explain the difference in the TGF-beta growth response. Further, evidence is presented for TGF-beta-stimulated p160ROCK translocation to the nucleus and inhibitory phosphorylation of the cyclin-dependent kinase-activating phosphatase, Cdc25A. The resultant suppression of Cdk2 activity contributes to G1/S inhibition in NMuMG cells. These data provide evidence that signaling through RhoA and p160ROCK is important in TGF-beta inhibition of cell proliferation and links signaling components for epithelial transdifferentiation with regulation of cell-cycle progression.

3T3 Cells↗

PubMed2003

Nocathiacins, new thiazolyl peptide antibiotics from Nocardia sp. I. Taxonomy, fermentation and biological activities.

Thiazolyl peptide antibiotics, nocathiacin I, II and III, were identified in a culture of Nocardia sp. WW-12651 (ATCC 202099). They exhibit potent in vitro activity (ng/ml) against a wide spectrum of gram-positive bacteria, including multiple-drug resistant pathogens such as methicillin-resistant Staphylococcus aureus (MRSA), multi-drug resistant Enterococcus faecium (MREF) and fully penicillin-resistant Streptococcus pneumoniae (PRSP), and demonstrate excellent in vivo efficacy in a systemic Staphylococcus aureus infection mice model.

Animals↗

PubMed2002

Preferential initiation of PC12 neurites in directions of changing substrate adhesivity.

When PC12 cells are grown on substrates showing a gradient of nonspecific adhesion, they preferentially initiate neurites in directions of changing adhesivity, whether that change is in the direction of increasing or decreasing adhesivity. This preference for changing adhesivity is ablated both by C. difficile toxin A, which inhibits all Rho-family GTPases, and by C. botulinum C3 exoenzyme, which specifically inhibits Rho.

ADP Ribose Transferases↗

PubMedDate not supplied

Menopausal Vasomotor Symptoms (MVS) survey for assessment of hot flashes.

OBJECTIVES: During the menopause, 65%-80% of women experience hot flashes. Hot flashes can also occur after hysterectomy and may be experienced during cancer therapy. A very limited assessment of hot flashes is provided by currently available menopausal instruments. This study was performed to evaluate a new Menopausal Vasomotor Symptoms (MVS) survey as an instrument for a comprehensive and subjective assessment of hot flashes. METHODS: The MVS survey was designed to assess multiple dimensions of hot flashes and to be simple and easy to administer. Hot flashes and associated conditions were addressed with 39 closed-ended questions. Sixty-one qualified women, 40-58 years old, from the Dallas, Fort Worth Metroplex area were enrolled. Women experiencing hot flashes took the survey at baseline and then 14 days, 2 months, and 6 months later. Factor analysis was performed. Face and content validity, internal consistency, test-retest reliability, and sensitivity to changes were evaluated. RESULTS: Fifty-two women (85.2%) completed all study sessions. The MVS survey was found to have good face and content validity and good internal consistency (rhoKR = 0.87). Spearman rank-order correlation coefficients at the 14-day retest varied from 0.58 to 1.00. As a result of these analyses, the MVS survey was further refined. CONCLUSIONS: The MVS survey was found to be comprehensive, simple, valid, reliable, sensitive, and a convenient instrument for subjective assessment of various characteristics of hot flashes. The MVS survey may serve as a valuable clinical and research tool for measurement of hot flashes.

Adult↗

PubMedDate not supplied

Long-term follow-up of patients treated for toxic epidermal necrolysis.

Patient outcomes concerning toxic epidermal necrolysis (TEN) have improved over the years as a better understanding of the pathophysiology of the illness has been gained and enhancements have been made in the care of the acutely ill. With increase in survival, long-term complications these patients experience are beginning to be recognized. In this study, we analyzed the outcomes of a cohort of TEN survivors treated at our burn unit and sought to determine the impact of clinical variables from the initial hospitalization on mortality after discharge. We performed a retrospective review of data from patients with TEN treated at our burn unit from March 1993 to September 2002. Follow-up data on new health problems were collected on patients who were alive at discharge via questionnaire. Survival was estimated using the Kaplan-Meier method with Cox regression model. During the study period, of the 64 patients treated for TEN, 46 survived. After discharge, 15 patients died, whereas the remaining 31 patients continued to suffer from ocular (54%), skin (81%), and renal (23%) problems. Median survival for the whole cohort has not been reached, with an estimated 5-year survival of 65%. No patient in either group had a TEN recurrence. Seventy-nine percent of the patients with ocular involvement in the acute phase of TEN had long-term ocular complications, and 73% of patients with mucosal involvement had persistent mucosal lesions. Five individual factors were found to be predictors of postdischarge mortality on univariate analysis: age at diagnosis of TEN>or=60 years, SCORTEN 3 to 6, % maximal TBSA slough>or=50%, days from onset of symptoms to admission to a burn unit>or=5 days, and presence of multiple comorbidities at diagnosis of TEN. In multivariate analysis, only SCORTEN of 3 to 6 (P=.003) and days to admission>or=5 (P=.027) maintained significance as predictors of mortality and may be used to heighten surveillance during postdischarge care of patients with TEN.

Adult↗

PubMedDate not supplied

Theory of mind may be contagious, but you don't catch it from your twin.

The theory-of-mind abilities of twins, children with nontwin siblings, and only children were compared to investigate further the link between number and type of siblings and theory-of-mind abilities. Three- to 5-year-old children with nontwin siblings outperformed both only children and twins with no other siblings, twins who also had other siblings outperformed twins who did not, and children with at least 1 opposite-sex sibling outperformed children with only same-sex siblings. Twins performed significantly better when asked about the false beliefs of their twins than they did when asked about the false beliefs of their friends. Results are discussed in terms of potential mechanisms that may account for the twin and sibling effects.

Child, Preschool↗